Álvarez-Cilleros David, Ramos Sonia, López-Oliva María Elvira, Escrivá Fernando, Álvarez Carmen, Fernández-Millán Elisa, Martín María Ángeles
Instituto de Ciencia y Tecnología de Alimentos y Nutrición (ICTAN-CSIC), Madrid, Spain.
Departamento de Fisiología. Facultad de Farmacia, Universidad Complutense de Madrid, Madrid, Spain.
Food Res Int. 2020 Jun;132:109058. doi: 10.1016/j.foodres.2020.109058. Epub 2020 Feb 1.
Cocoa supplementation improves glucose metabolism in Zucker diabetic fatty (ZDF) rats via multiple mechanisms. Furthermore, cocoa rich-diets modify the intestinal microbiota composition both in humans and rats in healthy conditions. Accordingly, we hypothesized that cocoa could interact with the gut microbiota (GM) in ZDF rats, contributing to their antidiabetic effects. Therefore, here we investigate the effect of cocoa intake on gut health and GM in ZDF diabetic rats. Male ZDF rats were fed with standard (ZDF-C) or 10% cocoa-rich diet (ZDF-Co) during 10 weeks. Zucker Lean animals (ZL) received the standard diet. Colon tissues were obtained to determine the barrier integrity and the inflammatory status of the intestine and faeces were analysed for microbial composition, short-chain fatty acids (SCFA) and lactate levels. We found that cocoa supplementation up-regulated the levels of the tight junction protein Zonula occludens-1 (ZO-1) and the mucin glycoprotein and reduced the expression of pro-inflammatory cytokines such as tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6) and monocyte chemoattractant protein 1 (MCP-1) in the colon of ZDF diabetic animals. Additionally, cocoa modulated the microbial composition of the ZDF rats to values similar to those of the lean group. Importantly, cocoa treatment increased the relative abundance of acetate-producing bacteria such as Blautia and prevented the increase in the relative amount of lactate-producing bacteria (mainly Enterococcus and Lactobacillus genera) in ZDF diabetic animals. Accordingly, the total levels of SCFA (mainly acetate) increased significantly in the faeces of ZDF-Co diabetic rats. Finally, modified GM was closely associated with improved biochemical parameters related to glucose homeostasis and intestinal integrity and inflammation. These findings demonstrate for the first time that cocoa intake modifies intestinal bacteria composition towards a healthier microbial profile in diabetic animals and suggest that these changes could be associated with the improved glucose homeostasis and gut health induced by cocoa in ZDF diabetic rats.
补充可可通过多种机制改善Zucker糖尿病脂肪（ZDF）大鼠的葡萄糖代谢。此外，富含可可的饮食在健康状况下会改变人和大鼠的肠道微生物群组成。因此，我们推测可可可能与ZDF大鼠的肠道微生物群（GM）相互作用，从而产生抗糖尿病作用。因此，我们在此研究可可摄入量对ZDF糖尿病大鼠肠道健康和GM的影响。雄性ZDF大鼠在10周内喂食标准饮食（ZDF-C）或10%富含可可的饮食（ZDF-Co）。Zucker瘦型动物（ZL）接受标准饮食。获取结肠组织以确定肠道屏障完整性和炎症状态，并分析粪便中的微生物组成、短链脂肪酸（SCFA）和乳酸水平。我们发现，补充可可上调了紧密连接蛋白闭合蛋白-1（ZO-1）和粘蛋白糖蛋白的水平，并降低了ZDF糖尿病动物结肠中促炎细胞因子如肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）和单核细胞趋化蛋白1（MCP-1）的表达。此外，可可将ZDF大鼠的微生物组成调节至与瘦型组相似的值。重要的是，可可治疗增加了产乙酸细菌（如布劳特氏菌属）的相对丰度，并防止了ZDF糖尿病动物中产乳酸细菌（主要是肠球菌属和乳杆菌属）相对数量的增加。因此，ZDF-Co糖尿病大鼠粪便中SCFA（主要是乙酸盐）的总水平显著增加。最后，改变的GM与改善的与葡萄糖稳态、肠道完整性和炎症相关的生化参数密切相关。这些发现首次证明，摄入可可可使糖尿病动物的肠道细菌组成朝着更健康的微生物谱改变，并表明这些变化可能与可可诱导的ZDF糖尿病大鼠葡萄糖稳态和肠道健康改善有关。
